Back to resultsPrebiotic Fibre Supplementation and Gut Microbiota in Non-alcoholic Fatty Liver Disease
Primary Purpose
Non-alcoholic Fatty Liver Disease
Status
Completed
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Prebiotic fibre
Placebo
Weight Loss
Sponsored by
About this trial
This is an interventional treatment trial for Non-alcoholic Fatty Liver Disease focused on measuring Dietary intervention, Prebiotic fibre, Weight loss, Gut microbiota, Obesity, Liver fat, Hepatic fibrosis
Eligibility Criteria
Inclusion Criteria:
- Adult subjects diagnosed with NAFLD on the basis of abnormal liver enzymes (ALT>1.5x upper limit of normal) and ultrasonography
- Exclusion of other causes of liver disease including viral hepatitis and alcoholic liver disease
- Aspartate aminotransferase and alanine aminotransferase ≤10x upper limit of normal
- Patients with type 2 diabetes treated with diet and exercise alone or metformin
Exclusion Criteria:
- Cirrhosis of the liver (FibroScan >17.5 kilopascal or FibroTest >0.8) or clinical features of cirrhosis.
- Alcohol consumption >20g/day (2 standard drinks) in women or > 30g/d (3 drinks) in men
- Alternate (e.g. TPN) or concomitant etiology for abnormal liver enzymes.
- History of decompensated liver disease including ascites, encephalopathy or variceal bleeding
- Concomitant use of any weight loss medication, previous bariatric or other intestinal surgery
- Presence of active infection, pregnancy or lactation
- Regular use of a probiotic or prebiotic supplement within 3 months prior to enrollment
- Antibiotic use within 3 months prior to enrollment
- Weight loss >3 kg within preceding 3 months to enrollment
- Uncontrolled cardiovascular or respiratory disease, active malignancy, or chronic infections
- Use of agents such as vitamin E, omega-3 fatty acids or medications with evidence for effects on NAFLD (pioglitazone, Glucagon-like peptide-1 analogues, dipeptidyl peptidase IV inhibitors, ursodeoxycholic acid)
- Patients with type 2 diabetes where HbA1c is >9%
Sites / Locations
- University of Calgary
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Other
Arm Label
Prebiotic Fibre
Placebo
Weight Loss
Arm Description
The intervention group will receive two 8g packets/day of prebiotic fibre to add to 250 ml of water and consume 30 minutes prior to breakfast and dinner.
The control group will receive two 3g packets/day of maltodextrin to add to 250 ml of water and consume 30 minutes prior to breakfast and dinner.
All participants will be supported through Registered Dietitian visits to achieve approximately 10% weight loss.
Outcomes
Primary Outcome Measures
Change in Liver Fat
Assessed via MRI
Change in Liver Fibrosis
Assessed via FibroScan (transient elastography)
Change in Liver Injury
Assessed via Fibrotest Score (composite score from serum biochemical markers: alfa2-macroglobulin, apolipoproteinA1, total bilirubin, haptoglobin, gamma glutamyl transpeptidase, alanine aminotransferase)
Secondary Outcome Measures
Change in Glucose Tolerance
Assessed via an oral glucose tolerance test
Change in Glycemic Control
Assessed via HbA1c
Change in Subjective Appetite
Assessed via Subjective appetite ratings on a visual analogue scale
Change in Satiety Hormones
Assessed in serum as pg/ml (Ghrelin, Glucagon-like peptide-1, Glucose-dependent insulinotropic polypeptide, leptin and Peptide tyrosine tyrosine)
Change in Body Composition
Assessed via dual x-ray absorptiometry
Change in Quality of Life
Assessed via the Short Form-36v2 Health Survey questionnaire
Dietary Adherence
Assessed via adherence to prescribed versus measured energy intake assessed by food records
Examine mechanisms related to prebiotic-induced changes in gut microbiota, their metabolic byproducts, and de novo lipogenesis
Via investigating gut microbiota shot-gun sequencing and measurement of volatile organic compounds and de novo lipogenesis using deuterium incorporation
Full Information
NCT ID
NCT02568605
First Posted
September 30, 2015
Last Updated
October 31, 2022
Sponsor
University of Calgary
Collaborators
Canadian Institutes of Health Research (CIHR)
1. Study Identification
Unique Protocol Identification Number
NCT02568605
Brief Title
Prebiotic Fibre Supplementation and Gut Microbiota in Non-alcoholic Fatty Liver Disease
Official Title
Prebiotic Fibre Supplementation and Gut Microbiota in Non-alcoholic Fatty Liver Disease
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
May 2015 (Actual)
Primary Completion Date
August 2019 (Actual)
Study Completion Date
August 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Calgary
Collaborators
Canadian Institutes of Health Research (CIHR)
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
Non-alcoholic fatty liver disease (NAFLD) is a condition where accumulation of fat in the liver leads to metabolic dysfunction. Currently there are no approved treatments for NAFLD. Part of the metabolic dysfunction may arise through changes in the gut microbiota. Prebiotic fibres have beneficial effects on glucose tolerance, body weight, and gut microbiota; therefore they may have potential as part of a dietary strategy for NAFLD treatment.
Detailed Description
The main objective of this study is to assess the effect of prebiotic fibre supplementation, in conjunction with diet-induced weight loss, on reduction in liver fat and injury.
Primary Objective - determine the change in hepatic injury (fibrosis and inflammation) and hepatic fat (percent fat) over 6 months in NAFLD patients treated with prebiotic or placebo during weight loss.
Secondary Objectives - determine the changes in appetite, body composition, glycemic and insulinemic responses, quality of life with prebiotic or placebo during weight loss, and examine mechanisms related to prebiotic-induced changes in gut microbiota and lipogenesis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-alcoholic Fatty Liver Disease
Keywords
Dietary intervention, Prebiotic fibre, Weight loss, Gut microbiota, Obesity, Liver fat, Hepatic fibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Prebiotic Fibre
Arm Type
Experimental
Arm Description
The intervention group will receive two 8g packets/day of prebiotic fibre to add to 250 ml of water and consume 30 minutes prior to breakfast and dinner.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The control group will receive two 3g packets/day of maltodextrin to add to 250 ml of water and consume 30 minutes prior to breakfast and dinner.
Arm Title
Weight Loss
Arm Type
Other
Arm Description
All participants will be supported through Registered Dietitian visits to achieve approximately 10% weight loss.
Intervention Type
Dietary Supplement
Intervention Name(s)
Prebiotic fibre
Intervention Description
Oligofructose-enriched inulin (Synergy1)
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Maltodextrin
Intervention Type
Behavioral
Intervention Name(s)
Weight Loss
Intervention Description
All participants will receive 10 one-on-one sessions with a Registered Dietitian designed to achieve 10% weight loss over 6 months. The sessions will focus on nutrition education and behavior counseling to reduce food intake and improve dietary quality.
Primary Outcome Measure Information:
Title
Change in Liver Fat
Description
Assessed via MRI
Time Frame
24 weeks
Title
Change in Liver Fibrosis
Description
Assessed via FibroScan (transient elastography)
Time Frame
24 weeks
Title
Change in Liver Injury
Description
Assessed via Fibrotest Score (composite score from serum biochemical markers: alfa2-macroglobulin, apolipoproteinA1, total bilirubin, haptoglobin, gamma glutamyl transpeptidase, alanine aminotransferase)
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Change in Glucose Tolerance
Description
Assessed via an oral glucose tolerance test
Time Frame
24 weeks
Title
Change in Glycemic Control
Description
Assessed via HbA1c
Time Frame
24 weeks
Title
Change in Subjective Appetite
Description
Assessed via Subjective appetite ratings on a visual analogue scale
Time Frame
24 weeks
Title
Change in Satiety Hormones
Description
Assessed in serum as pg/ml (Ghrelin, Glucagon-like peptide-1, Glucose-dependent insulinotropic polypeptide, leptin and Peptide tyrosine tyrosine)
Time Frame
24 weeks
Title
Change in Body Composition
Description
Assessed via dual x-ray absorptiometry
Time Frame
24 weeks
Title
Change in Quality of Life
Description
Assessed via the Short Form-36v2 Health Survey questionnaire
Time Frame
24 weeks
Title
Dietary Adherence
Description
Assessed via adherence to prescribed versus measured energy intake assessed by food records
Time Frame
24 weeks
Title
Examine mechanisms related to prebiotic-induced changes in gut microbiota, their metabolic byproducts, and de novo lipogenesis
Description
Via investigating gut microbiota shot-gun sequencing and measurement of volatile organic compounds and de novo lipogenesis using deuterium incorporation
Time Frame
24 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Adult subjects diagnosed with NAFLD on the basis of abnormal liver enzymes (ALT>1.5x upper limit of normal) and ultrasonography
Exclusion of other causes of liver disease including viral hepatitis and alcoholic liver disease
Aspartate aminotransferase and alanine aminotransferase ≤10x upper limit of normal
Patients with type 2 diabetes treated with diet and exercise alone or metformin
Exclusion Criteria:
Cirrhosis of the liver (FibroScan >17.5 kilopascal or FibroTest >0.8) or clinical features of cirrhosis.
Alcohol consumption >20g/day (2 standard drinks) in women or > 30g/d (3 drinks) in men
Alternate (e.g. TPN) or concomitant etiology for abnormal liver enzymes.
History of decompensated liver disease including ascites, encephalopathy or variceal bleeding
Concomitant use of any weight loss medication, previous bariatric or other intestinal surgery
Presence of active infection, pregnancy or lactation
Regular use of a probiotic or prebiotic supplement within 3 months prior to enrollment
Antibiotic use within 3 months prior to enrollment
Weight loss >3 kg within preceding 3 months to enrollment
Uncontrolled cardiovascular or respiratory disease, active malignancy, or chronic infections
Use of agents such as vitamin E, omega-3 fatty acids or medications with evidence for effects on NAFLD (pioglitazone, Glucagon-like peptide-1 analogues, dipeptidyl peptidase IV inhibitors, ursodeoxycholic acid)
Patients with type 2 diabetes where HbA1c is >9%
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raylene A Reimer, PhD, RD
Organizational Affiliation
University of Calgary
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Calgary
City
Calgary
State/Province
Alberta
ZIP/Postal Code
T2N 1N4
Country
Canada
12. IPD Sharing Statement
Plan to Share IPD
Undecided
Citations:
PubMed Identifier
26635079
Citation
Lambert JE, Parnell JA, Eksteen B, Raman M, Bomhof MR, Rioux KP, Madsen KL, Reimer RA. Gut microbiota manipulation with prebiotics in patients with non-alcoholic fatty liver disease: a randomized controlled trial protocol. BMC Gastroenterol. 2015 Dec 3;15:169. doi: 10.1186/s12876-015-0400-5.
Results Reference
derived
Learn more about this trial
Prebiotic Fibre Supplementation and Gut Microbiota in Non-alcoholic Fatty Liver Disease
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